Impact of a Patient-Centered Pharmacy Program and Intervention in a High-Risk Group

BACKGROUND: The medication therapy management (MTM) program identified high-risk members in a large employer group and invited them to participate in an MTM program. The intervention consisted of at least 3 consultations with a clinical pharmacist to review and discuss drug therapy. The goal was to improve drug therapy adherence and clinical outcomes. OBJECTIVES: To assess the impact of MTM on plan-paid health care costs, utilization of medical services, overall days supply of targeted medications, and medication possession ratios (MPRs). METHODS: The MTM and control group comprised eligible members of a large employer prescription benefit plan who were identified between October 1, 2007, and November 12, 2008, and invited to participate. Control group members were selected from targeted members who declined. After propensity score matching to ensure similarity of groups at baseline, each group had 2,250 members. Baseline comparisons and post-period impact analyses between groups were conducted using bivariate analysis. Post-period analyses used tests for paired comparisons. The MTM and control group members were studied for the year before and after their individual program invitations. We measured pre-post differences between the MTM members and controls in total heath care costs, inpatient visits, emergency room (ER) visits, total days supply, and MPRs for 5 conditions: diabetes, hypertension, dyslipidemia, depression, and asthma. RESULTS: MTM members significantly reduced their plan-paid health care costs by 10.3% or $977, compared with an increase of 0.7% or $62 in the control group (P=0.048). Inpatient visits in the MTM group decreased by 18.6%, while the control group experienced an increase of 24.2% (P  less than  0.001). While both groups had decreases in ER visits, the groups were not significantly different (P=0.399). Average days supply for the MTM group increased by 72.7 days over baseline; for the control group, it decreased by 111.1 days (P  less than  0.001). MTM members with hypertension and dyslipidemia had pre-post increases in MPR of 2.29% and 2.10%, respectively, while the control group had decreases of 2.31% and 2.61% (both P  less than  0.001). The mean MPRs for members with diabetes, depression, and asthma did not change in either group. Program costs per patient in 2009 were estimated to be $478. The program had a return on investment (ROI) of 2.0 in 2009. CONCLUSIONS: This study found that the pharmacist-managed MTM program to reconcile the medication therapies of high-risk patients and improve adherence, as measured by MPR, was effective in reducing total health care costs. The results show that those patients in the intervention group with hypertension and dyslipidemia had significant improvements in medication adherence, as compared with the control group. In fact, the intervention group used significantly more days of therapy in the intervention period, and the control group used significantly fewer days than either group used during the baseline period. MTM interventions were associated with a significant decrease in the MTM members’ overall plan-paid health care costs, driven largely by decreases in inpatient utilization and mediated by increases in average days supply and in MPR increases for hypertension and dyslipidemia. Overall, the MTM program was cost-effective. The ROI estimated for this program of 2.0 is only slightly lower than the average disease management ROIs reported in the literature.

• A recent summary of the literature on the effectiveness of medication therapy management (MTM) programs included only 11 studies; small sample sizes and research design issues were identified as problems. It found that MTM programs were often associated with clinical improvements, but studies on utilization of medical services and medications were mixed. The review noted in particular that there have been few published studies conducted by pharmacy benefit managers (PBMs) or Medicare Part D programs and that few studies report program costs along with program savings. • One PBM MTM study reported on the effectiveness of an intervention in which a letter about statin initiation was sent to the prescribers of patients with diabetes or coronary artery disease.
With an intervention group of 1,144 members and a control group of 700, the study found a highly significant improvement in statin initiation rates for the intervention group. • Several highly focused pharmacist-managed programs for specific disease conditions or medications have reported significant improvements over the current standard of care. For example, a retrospective study of pharmacist-provided MTM services to Medi-Cal patients with human immunodeficiency virus or acquired immune deficiency syndrome had a large study population, with 1,353 patients receiving interventions and 5,665 control group patients. This study reported a highly significant impact on adherence.
awareness of medication-related problems coupled with regulatory agencies' requirements and potential penalties, health care providers are actively seeking effective solutions to improve medication outcomes and reduce adverse events. Hospitals are increasingly implementing focused programs to assist patients post-discharge to avoid Medicare reimbursement reductions if their 30-day hospital readmission rates exceed a calculated risk-adjusted level. 11 However, a recent review of studies to prevent rehospitalization within 30 days found that various interventions, including medication reconciliation at discharge, were inconsistent in reducing readmissions. 12 A recent summary of the literature on the effectiveness of MTM programs included only 11 studies, and while some showed positive or mixed results, small sample sizes and research design issues require additional research. 13 This review also noted that there have been few published studies of MTM programs conducted by pharmacy benefit managers (PBMs) or Medicare Part D programs and that few studies report program costs along with program savings. Evaluations of disease management programs have been more numerous and illustrate challenges faced by MTM programs as well as disease management programs. The evaluation of disease management programs administered by TRICARE for the Military Health System reported modest reductions in hospitalizations and medical costs while achieving a positive return on investment. 14 However, a rigorous study of 15 diverse disease management-like programs to coordinate care and control health care costs for high-cost Medicare patients with heart failure, coronary artery disease, or diabetes found that only 2 of the 15 programs reduced intervention group hospitalization as compared with the control group, using P < 0.10 as the threshold for significance. 15 None of the 15 programs significantly reduced intervention group expenditures or achieved a positive return on investment when including program costs. The 2 programs with large, if not statistically significant, cost reductions for the intervention group were also notable for having a significantly greater proportion of patients who received educational interventions on how to take their medications. Educating patients on how to take their medications is also a component of our MTM intervention.
While disease management programs have a broad focus on general health, diet, and exercise, MTM programs are focused on reconciling medication regimens, preventing adverse events, identifying significant medication interactions and missing essential therapies, and improving adherence. Informing patients of specific small steps to improve health creates a more educated patient and improves dialogue opportunities with providers. 3 Several highly focused pharmacist-managed programs for specific disease conditions or medications have reported significant improvements over the current standard of care. 16,17 One MTM program conducted by a PBM company reported the effectiveness of an intervention in which letters A ppropriate medication therapy remains one of the most cost-effective treatment options in health care today. 1 However, medication therapy involves some risk of causing an adverse event. 2 The elderly are at the highest risk for adverse drug events because of the burden of multiple conditions. 3 The average number of medications used by patients aged 65 and older was 6.3 distinct medications in 2006. 4 Each additional medication increases the risk of an adverse event by about 10%, according to 1 study. 5 With the increased complexity of therapy options and the aging of the population, medication therapy management (MTM) support is often necessary to ensure a desired outcome of a patient's drug therapy. 3 In addition to adverse drug events, other medication therapy concerns include indication, ineffective therapy, the absence of appropriate therapy, and poor adherence. Many elderly patients receive complex medication regimens from multiple providers, often without coordination and communication among them. 6 New studies on the challenges of medication reconciliation identified that both hospitals and ambulatory care clinics have difficulty obtaining accurate information on patients' complete medication profiles. [7][8][9] Even the medication list derived from pharmacy claims is incomplete because of the lack of information on over-the-counter medications and nutritional supplements, which need to be considered to avoid adverse events. 10 Strategies to improve patient-provider communication about medication therapy such as the program described here are essential to ensure positive outcomes and prevent unwanted adverse effects. Our program develops a comprehensive medication profile through the use of prescription claims, lab data, over-the-counter medications, and nutritional supplements along with patient input on lifestyle choices. With the growing • MTM intervention strongly impacted hospitalization risk in the post-period. With no significant difference between the 2 groups in the baseline period, in the post-period the intervention group had only 28.7% of patients with an admission, compared with 38.1% of control group patients (P = 0.001). • MTM intervention strongly impacted post-period medication possession ratios (MPRs) for hypertension and dyslipidemia. While there were no significant differences in baseline MPRs for these conditions, post-period MPRs for the intervention group increased by 2.29% for hypertension and 2.10% for dyslipidemia, while post-period MPRs for the control group decreased by 2.31% and 2.61% (P < 0.001), giving the intervention group a lift of more than 4% over the control group. • The total health care savings per patient due to program impact was estimated to be $977, with program costs per patient of $478, yielding a return on investment (ROI) of 2.0 in 2009.

What this study adds (continued)
were sent to prescribers of patients with diabetes or coronary artery disease notifying them of patients that did not fill a statin prescription in the last 6 months and asking if statin initiation could be considered with the intent of closing a therapeutic gap and increasing adherence. 18 This study, with an intervention group of 1,144 members and a control group of 700, found a highly significant improvement in statin initiation rates for the intervention group. Another PBM reported increasing adherence rates by 2.1% in patients with diabetes and adding missing therapies through pharmacist outreach at both the retail and mail pharmacies. 19 The objective of our study was to assess the impact of MTM on plan-paid health care costs, utilization of medical services, overall days supply of targeted medications, and medication possession ratios (MPRs).

■■ Methods Description of the Pharmacist Intervention
After a pilot program during 2004-2006, the MTM program was launched in August 2006 to improve drug therapy outcomes by providing high-risk patients with one-on-one medication counseling. The setting for this study was national. Medication counseling was provided over the telephone by specially trained clinical pharmacists located in the central clinical services office of a large PBM company. Patients were targeted if they were over the age of 18 and had 14 or more claims within a 120-day period and/or had claims showing the absence of a recommended therapy or the presence of a conflicting therapy in the treatment of conditions such as, but not limited to, asthma, diabetes, heart failure, or heart disease. Patients were sent a letter inviting them to enroll, an electronic medical record was created, and a scheduled telephonic appointment with a pharmacist was made. Patients were encouraged to fax or mail validated lab data in advance of the initial appointment to guide in the assessment of medication appropriateness, effectiveness, and safety. During the initial telephonic visit, the clinical pharmacist reviewed the patient's drug therapies, including nonprescription medications and nutritional supplements; medical conditions; allergies; any adverse drug reactions; social behaviors such as tobacco and alcohol use; and key lab values. The primary focus of the initial appointment was to review the patient's medical conditions and medications, address the patient's primary drug therapy concerns, and discuss any major drug therapy issues identified through the review. Each medication was reviewed for indication, effectiveness, safety, and adherence. The indication or appropriate use of a medication was determined based on treatment guidelines, U.S. Food and Drug Administration (FDA)-approved indications, validated lab data where appropriate, and patient input on conditions and symptoms. Following each appointment, the clinical pharmacist prepared an individualized care plan for the patient. The care plan included drug therapy issues discussed, specific recommenda-tions for therapy, and any action items for the patient to share with his or her health care provider. If appropriate, the clinical pharmacist would ask the patient if he or she would like the pharmacist to fax the care plan to the provider. For patients referred by case or disease managers, the care plan was automatically shared with the referring party and an offer was made to call the provider on more urgent issues. The patients were mailed 2 copies of the care plan, which included a complete list of their prescription medications, over-the-counter medications, and herbal and vitamin supplements. The care plan was intended to enhance the patient's conversation with his or her health care provider at the next visit and included the contact information for the pharmacist in the event the treating provider had follow-up questions.
Follow-up telephone appointments were scheduled to meet the needs of individual patients and usually included 2 or more additional visits over the course of a year. To ensure continuity of care, patients spoke with the same clinical pharmacist for all visits when possible. Patients were also encouraged to call their personal clinical pharmacists with any immediate questions or concerns, especially questions pertaining to newly prescribed medications. Therefore, the overall program intervention consisted of at least 3 consultations with a clinical pharmacist to review and discuss drug therapy within 12 months of the date the patient enrolled in the program.

Study Objectives
The primary purpose of this study was to assess the impact of the pharmacist intervention program on plan-paid health care costs. The study used pharmacy and medical claims data to describe and compare the patients enrolled, and those not enrolled, in the intervention program with respect to (a) patient characteristics; (b) intermediate outcomes, including conditionlevel MPRs as a measure of adherence; (c) pharmacy and medical utilization; and (d) plan-paid medical and pharmacy costs.

Outcome Measures
The main outcome measure was the plan-paid total heath care costs for each patient. Plan-paid health care cost was the sum of plan-paid pharmacy costs and plan-paid total medical costs calculated for both baseline and intervention periods. Patientpaid costs were not included. A secondary outcome measure was the condition-level MPR between the baseline and intervention periods for each patient. MPR was defined as the total days supply the participant had available during the baseline or intervention period, divided by 365 days, and weighted by each drug class used for the condition. Definitions of the patient-level outcome measures are summarized in Appendix A. Five conditions were identified from pharmacy claims using standard drug codes: diabetes, hypertension, dyslipidemia, depression, and asthma (Appendix B).

Study Design and Patient Selection
The study design was a retrospective cohort study of utilization and cost changes for patients in a pre-post intervention with a matched control group taken from a large employer group. Patients were invited by letter to participate in the program between October 1, 2007, and November 12,2008. Patients who accepted the MTM invitation and met at least 3 times with a clinical pharmacist for drug therapy review were identified as the intervention group (n = 2,966). The baseline or pre-period was 365 days preceding the patient's program invitation date, and the intervention or post-period was 365 days following the patient's program invitation date. Patients who did not accept the invitation during this period were part of the control group pool (n = 10,126). To address the potential bias of a self-selected control group, propensity score matching was used to match the control group on a one-to-one basis to the intervention group using the following matching characteristics: age, gender, baseline days supply, baseline plan-paid pharmacy costs, baseline plan-paid medical costs, physician visits, inpatient visits, outpatient visits, and number of pharmacy-derived conditions. Patients were not matched on specific conditions such as diabetes or hypertension. Emergency room (ER) visits could not be matched without an excessive loss of patients in the intervention group. A sensitivity analysis was conducted to assess the impact of not matching on this important factor. A separate propensity matching exercise that retained ER visits was conducted. The smaller subset of patients who were matched was analyzed, and the primary outcome measure of the difference in pre-post total plan-paid health care costs was assessed by paired t-tests. The results were similar in size, direction, and significance level to the results for the larger group. It was decided to use the larger matched population for increased face validity. Figure 1 summarizes this group selection process.

Data Analysis
Descriptive statistics were calculated for all variables. Baseline differences between the intervention group and control group were tested using t-tests for continuous variables and chi square tests for categorical variables (Table 1). Pre-post changes in costs and utilization were assessed by paired t-tests. Pre-post changes in MPR were also assessed by paired t-tests. Statistical significance was set at P < 0.05. All statistical analyses were performed using SAS version 9.1 (SAS Institute, Cary, NC).

Baseline Comparisons
The matched study population consisted of 4,500 patients. Both the intervention group and the matched control group had an average age of 74, with 60% female. Average plan-paid pharmacy costs in the baseline year were $4,853 for the intervention group and $5,081 for the control group (P = 0.242). There were no significant differences in average baseline days supply between the intervention and control groups (2,708 vs. 2,716; P = 0.815). However, the groups differed significantly on the average number of prescriptions filled (55.3 vs. 69.2; P < 0.001). This divergence is explained by the intervention group's significantly greater baseline use of mail order pharmacy services (35.5% vs. 19.1%; P < 0.001). The intervention group's lower member copayment average is also explained by the difference in mail use, as the mail service incentive is a lower copayment. The average number of baseline ER visits also differed significantly between the intervention and control groups (0.7 vs. 0.8; P = 0.016). The number of conditions per person was the same in both groups (2.5; P = 0.883; Table 1). Also, the distribution of patients by the number of conditions was not significantly different between groups (P = 0.793; full results not shown). However, there were significantly more patients with diabetes (P = 0.010) or depression (P = 0.001) in the control group, and significantly fewer patients with dyslipidemia (P < 0.001; Table 1). There were no significant differences between the intervention and control groups in baseline MPRs for the target conditions ( Table 1).

Comparisons of Pre-Post Differences
As a primary outcome, the intervention group members significantly reduced their plan-paid health care costs by 10.3% or $977 in the post-period, compared with an increase of 0.7% or $62 in the control group (paired t-test; P = 0.048; Table 2).
Secondarily, the pre-post differences in health care utilization were significant except where noted. The intervention Members aged 18 or older with at least 14 pharmacy claims in a 120-day period who were offered the program between October 1, 2007, and November 12, 2008, and who had continous eligibility for 12 months before and after the program invitation date N = 13,092 Exclusions: Members with medical utilization services but no recorded medical plan payments due to dual coverage and coordination of benefits n = 8,723 Enrolled in program n = 2,260 Declined program n = 6,463 Intervention group members matched to control group members n = 2,250 Control group members matched to intervention group members n = 2,250

FIGURE 1
Group Selection Process group had a substantial increase in total days supply of medication of almost 73 additional days, in contrast to the control group's sharp decrease of 111 days (P < 0.001). Inpatient visits in the MTM group decreased by 18.6%, while the control group experienced an increase of 24.2% (paired t-test; P < 0.001; Table  2). Regular physician visits to renew medications and monitor health status were vital to the chronically ill older population. The intervention group had a small but statistically significant decrease in physician office visits, declining from 27.7 to 27.0 visits per patient per year, or 2.5% from baseline (P = 0.010). In contrast, the control group had a much larger decrease from 27.2 to 24.0, a decline of 3.2 visits, or 11.8% from baseline (P < 0.001). The intergroup comparison of pre-post differences in physician office visits was significant (paired t-test, -0.70 vs. -3.1; P < 0.001; Table 2). Program intervention was associated with a smaller pre-post reduction in the use of physician office visits as compared with the control group. The intervention group had a nonsignificant decrease in ER visits, decreasing from an already low 0.66 to 0.63 visits (P = 0.225), while the control group started higher and decreased from 0.76 to 0.69 (P = 0.026). The intergroup comparison of pre-post differences in ER visits was not significant (paired t-test, 0.037 vs. 0.076; P = 0.399; Table 2). Additional analysis was performed on the percentage of members who were hospitalized because of the importance of the reductions in inpatient utilization. There was no significant difference between the intervention group and the control group in the proportion of patients with at least 1 inpatient stay in the baseline period (P = 0.273; Table 3). In the postperiod, the intervention group had only 28.7% of patients with at least 1 inpatient stay, compared with 38.1% of control group patients (P < 0.001; Table 3). Analysis of the intragroup pre-post changes was conducted using the McNemar test to account for paired observations. The findings confirmed the significant reduction for the intervention group and identified a significant increase for the control group (Table 3).

Results: Pre-Post Changes in Key Metrics
group used significantly fewer days, as compared with the number of days each group used during the baseline period. Numerous studies have associated higher levels of adherence with better health outcomes and lower costs. However, Roebuck et al. (2011) used a robust fixed-effects methodology to adjust for the disadvantages of observational studies and estimate a causal relationship. This study found that improved medication adherence produced substantial decreases in total health care costs as a result of reductions in hospitalization and ER use. 20 While the primary intervention conducted by this MTM program was medication reconciliation, increased adherence was encouraged. The significant improvement in adherence in 2 conditions, hypertension and dyslipidemia, as well as the nonsignificant increases in the other conditions, resulted in increased pharmacy costs, which were offset by reductions in medical costs. The comprehensive MTM intervention, including the focus on medication reconciliation and adherence, resulted in a significant impact on total plan-paid health care costs.
Overall, the MTM program was cost-effective. The ROI estimated for this program of 2.0 is lower than the average disease management ROIs of 2.8, summarized by Dall et al. (2010), but higher than the 1.26 ROI that Dall reported in the evaluation of the TRICARE disease management programs. 14 While our program was focused on comprehensive medication management and not disease management more broadly, few evaluations of MTM have published ROI results for comparative purposes. 9 It is difficult to compare results across programs, since the types of interventions vary substantially across programs, and patient disease mix and severity differ widely. However, this report supports the conclusion that this patient-centered MTM program was cost-effective. As it is one of the largest MTM programs reported in the literature with 2,250 patients receiving interventions, this study adds to the body of literature showing that pharmacist counseling can be effective in improving medication therapy and adherence and lowering total health care costs.

Limitations
The foremost limitation of this study was self-selection. Patients were invited to participate in the MTM counseling program based on high utilization in the past and the potential for continued high utilization. Of the 13,092 patients invited to participate in a free telephone-based counseling program with a pharmacist, only 22.6% accepted. The patients who declined to participate formed the control group pool from which patients matching important characteristics of a patient in the intervention group were selected. However, it is possible that the patients who chose to participate were different in some immeasurable characteristic that contributed more to the actual change in cost and utilization outcomes that occurred than the pharmacist counseling. Important utilization changes were also reflected in changes in MPR. The intervention group had significant pre-post increases in MPR for hypertension and dyslipidemia, while the control group had significant decreases. While none of the other conditions had significant changes, the intervention group tended to have increases, while the control group showed little change.
The MPR findings were confirmed with linear regression showing the intervention group had a significant lift in postperiod MPRs of over 4% for hypertension and dyslipidemia, as compared with the control group, while controlling for baseline characteristics (P < 0.001). The intervention group decreased its use of more expensive medical services, such as inpatient hospitalization, at the same time as it significantly increased pharmacy utilization with only a small decrease in physician office visits. The program intervention served to support increased adherence to medication, which itself could serve as the means through which lower hospital utilization may have been achieved.
Program costs per patient in 2009 were estimated to be $478. The plan-paid health care savings per patient due to program impact but not reduced by program costs was estimated to be $977. The program had a return on investment (ROI) of 2.0 in 2009.

■■ Discussion
This study found that the pharmacist-managed MTM program to reconcile the medication therapies of high-risk patients and improve adherence was effective in reducing total health care costs. The program significantly reduced hospitalizations in the intervention group, in contrast to a significant increase in hospitalizations in the control group. The intervention group had a reduction of 15% in inpatient utilization, while the control group had an increase of 7.6%. In addition, results show that patients in the intervention group had significant improvements in medication adherence, as compared with the control group. In fact, the intervention group used significantly more days of therapy in the intervention period, while the control

■■ Conclusions
This evaluation report found that the participants in this patient-centric, high-touch MTM program significantly increased their medication adherence levels and reduced their use of inpatient hospital services, as compared with a matched control group. Overall program impact showed a significant decrease in total plan-paid health care costs even with the increase in the utilization and costs of pharmacy benefits. Results show that patient outcomes can be improved through one-on-one medication counseling by specially trained clinical pharmacists.
A second limitation was that 192 of the 2,250 patients in the intervention group entered the program as referrals, while none of the control group was referred. Only 40 of the 192 (21%) were referred by a case or disease-management program, while the remaining patients were referred by their family or friends. Baseline characteristics of the referred patients and the rest of the intervention group were compared. In comparison to the rest of the intervention group, the referred patients were not significantly different in age (74.2 vs. 74.1; P = 0.862) or in percentage of female participants (58.9% vs. 60.9%; P = 0.582). However, they had significantly fewer conditions per person (2.0 vs. 2.5; P < 0.001). Similarly, they had significantly fewer baseline prescriptions (34.7 vs. 56.1; P < 0.001) and significantly fewer total days supply of medication (1,879.2 vs. 2,732.3; P < 0.001), but they were not significantly different on ER visits (0.49 vs. 0.45; P = 0.341) or on plan-paid medical costs ($2,858 vs. $3,860; P = 0.259). Overall, the referred patients appeared to have a lower burden of disease than the rest of the intervention group. Referral status was ignored in the analysis. Outcomes were also reviewed to assess whether substantial differences were revealed. Referred patients had outcomes similar to the rest of the intervention group. The referred group showed a significant increase in days supply (87.8; P = 0.022) as did the rest of the intervention group (71.3; P < 0.001). While they had a decrease in total health care costs, it was not significant (-$484; P = 0.722). In contrast, the rest of the intervention group had a significant decrease (-$1,023; P = 0.006). The decision to ignore the referral status appeared to have no impact on the overall direction of the outcomes of the study.
A third limitation was that information on patient participation in other care management programs was unavailable. We assumed that any participation that did occur was evenly distributed among both the intervention and control groups.
A potential limitation was the lack of ability to match the intervention and control groups simultaneously on prescription count and total days supply. The groups were matched on total days supply, resulting in a significant baseline difference in the number of prescriptions filled. This divergence between the number of prescription fills in both groups with no significant differences between days supply was explained by the intervention group's significantly greater baseline mail distribution rate (35.5% vs. 19.1%; P < 0.001). Mail prescriptions generally provide a 90-day supply and retail a 30-day supply. The mail distribution rate was significantly correlated with intervention group status and was not useable as a predictor variable in regression analysis. Some studies have linked intergroup adherence differences with mail distribution rates. 21,22 However, as baseline adherence was similar between the intervention and control groups, mail utilization was considered to have no impact on the pre-post utilization differences.